Researchers have discovered an important clue about how cancer cells manage to locate and enter the lymphatic system - an important part of the immune system - as a way to travel to new sites to form secondary tumors.
Writing in the journal Oncogene, cancer researchers and immunologists led by the Karolinska Institutet in Stockholm, Sweden, describe how they found cancer cells "disguise themselves" as white blood cells to gain entry to the lymphatic system.
The team suggests the discovery should help develop new drugs to prevent or reduce cancer spread through the lymphatic system.
Metastasis - where cancer spreads to other parts of the body - is the major cause of death from cancer. Cells break off from the primary tumor and travel through the body to set up secondary tumors in vital organs such as the lungs or the liver.
The lymphatic system is a network of nodes and vessels that runs throughout the body. It is an important part of the immune system that helps fight bacteria and other infections and to dispose of old and abnormal cells.
Cancer cells frequently use the lymphatic system to travel to other parts of the body. In breast cancer, for example, swollen lymph nodes are often the first sign of metastasis, and invasion of lymph vessels is usually a better prognostic marker than invasion of blood vessels.
However, it is not clear how tumor cells find their way to lymphatic vessels, as lead investigator Jonas Fuxe, an associate professor in medical biochemistry and biophysics at Karolinska Institutet, explains:
"It's not clear whether there are signals controlling this or whether it's just random. However, in recent years it has become evident that inflammation is a factor that can promote metastasis and that anti-inflammatory drugs may have a certain inhibitory effect on the spread of cancer."
TGF-beta gives cancer cells receptors that guide them to lymphatic system
In their paper, Prof. Fuxe and colleagues describe how they found an inflammation protein called TGF-beta (transforming growth factor-beta) can make cancer cells partially take on the guise of immune cells.
TGF-beta supplies the surface of the cancer cells with a receptor normally only displayed by the white blood cells that frequent the lymphatic system.
The "gifted" surface receptors cause the cancer cells to be attracted toward changing concentrations of a substance that binds to the receptors after secretion from lymphatic vessels.
The result is an effective way of targeting lymphatic vessels and migrating to lymph nodes - in the same way as immune cells.
The team believes the finding reveals a link between inflammation and cancer not seen before - a deeper understanding of which may open new avenues for treatment.
Prof. Fuxe says they would now like to find out if cancer cells take on any other immune cell features to enhance their ability to trick the lymphatic system, and how these affect the process of metastasis. He concludes:
"The possibility of preventing or slowing down the spread of cancer cells via the lymphatic system is an attractive one, as it could reduce the risk of metastasis to other organs."